S1PR4 p.Pro115=
c.345C>T · rs373222281 · VCV2648986
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0522%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9.6 | GERP -3.6 |
| Overall | ||
| CADD | 3.224 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0522%
European (non-Finnish) · 616/1,179,666 alleles
Filtering AF
0.0487%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0474%
Overall
0.0399%
643/1,611,912 alleles · ultra-rare
exomes 594/1,459,550 · genomes 49/152,362 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0522% | 1,915 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,903 |
| African / African-American | 0.00666% | 15,013 |
| Finnishnot grpmax-eligible | 0.00481% | 20,772 |
| Admixed American | 0.00333% | 30,000 |
| South Asian | 0.0011% | 91,032 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- S1PR4
- Protein
- p.Pro115=
- Coding
- c.345C>T
- MANE Select
- NM_003775
- dbSNP
- rs373222281
- Type
- single nucleotide variant
- Location
- chr19:3179137 (GRCh38)
- Gene constraint
- LOEUF 1.894 · pLI 0.16 (gnomAD)
- Structure
- AlphaFold pLDDT 78.44 · 1 PDB
- Residue 115
- a β-strand
Similar variants
- S1PR4 p.Thr95= Benign/Likely benign ★★ same type
- S1PR4 p.Ala101Thr Uncertain significance ★ ⚠ same type
- S1PR4 p.Ala114Thr Uncertain significance ★ ⚠ same type
- S1PR4 p.Ala116Thr Uncertain significance ★ ⚠ same type
- S1PR4 p.Ala116Val Uncertain significance ★ ⚠ same type
- S1PR4 p.Ala128Thr Uncertain significance ★ ⚠ same type
- S1PR4 p.Ala130Thr Uncertain significance ★ same type
- S1PR4 p.Ala131Thr Uncertain significance ★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/s1pr4-p-pro115 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown